RNAi silencing of exogenous and endogenous reporter genes using a macrocyclic octaamine as a "compact" siRNA carrier. Studies on the nonsilenced residual activity

Kazuki Matsui, Shohei Horiuchi, Shinsuke Sando, Takashi Sera, Yasuhiro Aoyama

Research output: Contribution to journalArticle

15 Citations (Scopus)


A macrocyclic octaamine 1 having a covalently linked lipid-bundle structure was introduced as a new type of siRNA carrier. Gel electrophoresis, DLS, and SPR results indicate that it strongly binds to a luciferase-targeting 21-mer (42P) siRNA with a ratio of 1/P ≅ 0.3 (1/N ≅ 2.4) to give remarkably compact 1-siRNA complexes with an average size of ∼10 nm. The 1-mediated siRNA silencing of the exogenous luciferase gene occurs with a 90-95% efficiency. The overall suppression-[siRNA] profile with a 5-10% residual activity in the saturation region is commonly observed irrespective of the cell type (HeLa, HepG2, or HEK293), the order, or timing (stepwise or simultaneous) of supply of the siRNA and that of the luciferase-encoding plasmid, the level of mRNA transcribed, or the type of carriers (1 vs lipofectamine 2000). The silencing of the endogenous DsRed2 gene stably incorporated in the genome of HeLa cells also has a similar overall profile. These results suggest that (1) the cellular uptake of the plasmid and that of the siRNA are basically independent of each other and (2) the incomplete silencing is not due to insufficient siRNA delivery. Implication of item 2 is briefly discussed.

Original languageEnglish
Pages (from-to)132-138
Number of pages7
JournalBioconjugate Chemistry
Issue number1
Publication statusPublished - Jan 2006
Externally publishedYes


ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

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